Novel series of long chain isoxazole derivatives were designed as inhibitors of Cytochrome P450-14DM14a-demethylase from Candida albicans and ribosomal subunit of S12 protein from Escherichia coli. The novel compounds (6-10) were synthesized through 1,3-dipolar cycloaddition of nitrile oxide to long chain alkynoic acid and alkenyl/hydroxyalkenyl esters and tested for their antimicrobial activity by disk diffusion assay and MIC by broth micro dilution method. After predicting the hidden potential and drug-likeness of compounds, ADMET-related descriptors were also calculated to predict pharmacokinetic properties. Molecular docking studies have been performed to evaluate possible mode of action of molecules in active site of receptor. Compounds (9 and 10) showed excellent antimicrobial activity nearly equivalent to the control compounds.